The concept of recognizable oral potentially malignant disorders has arisen following a number of salient clinicopathological observations and the realization that numerous histopathological and biomolecular tissue changes are common to both cancers and their potentially-malignant counterparts. Oral leukoplakia and oral-submucous-fibrosis are the most common oral-mucosal diseases of the potentially malignant spectrum having high prevalence in Indian population with significant malignant transformation rates. Being chiefly habit associated, these can be promptly treated. Leukoplakia is characterized by impairment of epithelial differentiation program. Although multifactorial, tobacco has been commonly implicated in its pathogenesis. Cofactors affecting prognosis include association with Candida, HPV; Parameters like Loss-of-heterozygosity(LOH), aneuploidy, mutation in tumor-suppressor-genes(TSG‟s), expression of tissue markers, and upregulation of cyclinD1, Matrix-metalloproteinases(MMP‟s), telomerase activities reflect oncogenic potential. Oral submucous fibrosis is a chronic progressive disorder with juxta-epithelial fibrosis as hallmark of the disease. Originally an idiopathic condition, its etiopathogenesis today is multifarious. Arecanut (alkaloids,copper,polyphenols), micronutrient deficiencies, autoimmunity, equilibrium shift amongst inflammatory cytokines, cell-cycle alterations , inactivation of oncosuppressor-genes, activation of angiogenic factors contribute to the development, progression and carcinogenesis in varying capacities. Addressing the above mechanisms will help in preventing progression of disease, risk stratification, delivering targeted therapy and improving overall prognosis.